The pathophysiology of acute, persistent and reactivation infection with varicella zoster virus (VZV) is poorly defined. Clinical studies of varicella have demonstrated that infection can be acquired by the nasopharyngeal route and suggest that low level viremia occurs prior to the development of exanthem. In the immunocompromised host with progressive VZV infection, cell-associated viremia occurs in conjunction with exanthem. Clinical and pathologic studies of patients with herpes zoster have implicated the sensory neuroganglia as a probable site of persistent viral infection. Studies of VZV infection have been hampered by the lack of a suitable animal model of VZV infection. We have demonstrated that guinea pigs exposed to guinea pig-adapted VZV develop nasopharyngeal viral replication, viremia, the production of specific humoral antibody and the development of exanthem. Airborne transmission of VZV to cagemates has also been observed. In the research outlined in this application, we propose to explore the guinea pig as a model of acute, persistent and recurrent VZV infection. We will characterize the acute infection in normal and immunologically modified guinea pigs and determine if persistent or latent infection occurs. In addition, we propose to expand our clinical observation and define the viremia hypothesized to occur during varicella incubation and which may occur in some patients with herpes zoster. Both aspects of this proposal will permit examination of the specific immunologic parameters of VZV infection.